A University of Alberta research team has found a genetic variant that can be used to identify which patients with pulmonary arterial hypertension need the most urgent care.
“This could potentially save lives and health-care costs, and improve the well-being of both patients and their loved ones,” says principal investigator Evangelos Michelakis, professor and associate chair of research for the Department of Medicine and director of the Cardiovascular Research Institute.
Pulmonary arterial hypertension (PAH) affects thousands of Canadians, according to the research team. PAH is caused by an overgrowth of cells in the wall of the lung arteries, leading to obstruction of blood flow and exhaustion of the right chambers of the heart as they struggle to pump blood through the lungs.
Fifty per cent of patients die within five years of diagnosis, a prognosis similar to metastatic breast cancer. While there are some drug treatments, they’re very expensive and do not necessarily prolong life or reverse the disease. Heart transplant is often the only effective intervention, but many patients deteriorate before they get a transplant.
Some patients with PAH develop heart failure much sooner than others, but until now the cause has been unknown.
In newly published research in the American Heart Association’s journal Circulation, the Michelakis team identified a gene variant in about 30 per cent of patients that predicted early failure of the right heart chambers.
The team tested rats and heart tissue from three patient groups at the U of A, Laval University and Duke University, finding that patients carrying this genetic variation were predisposed to faster decompensation of their right heart chambers compared with non-carriers.
They also found that patients with more inflammation decompensated early, noting that many patients with PAH also suffer from inflammatory diseases such as scleroderma or lupus.
The next step will be to reproduce the results in larger populations. The ultimate goal would be to make a test available to identify high-risk patients who could be given more intense treatment, more frequent followup and earlier referral for transplantation.
“Because it is easy to detect this genetic variant using a mouth swab, and we can detect inflammation through a blood test and by taking the medical history, we hope our team’s findings can quickly change medical practice,” Michelakis says.
The U of A researchers collaborated with teams at Laval and Duke universities. The work was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the University Hospital Foundation.